June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
Identifying and classifying nonspecific orbital inflammation (NSOI) by gene expression array
Author Affiliations & Notes
  • James Rosenbaum
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
    Devers Eye Institute, Legacy Research Institute, Portland, OR
  • Dongseok Choi
    Public Health and Preventive Medicine, Oregon Health & Science University, Portland, OR
  • Christina Harrington
    Integrated Genomics, Oregon Health & Science University, Portland, OR
  • Gerald Harris
    Department of Ophthalmology, Medical College of Wisconsin, Milwaukee, WI
  • Craig Czyz
    Department of Ophthalmology, Ohio University, Columbus, OH
  • Valerie White
    Department of Pathology, University of British Columbia, Vancouver, BC, Canada
  • Eric Steele
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Bobby Korn
    Department of Ophthalmology, University of California, San Diego, CA
  • David Wilson
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Stephen Planck
    Casey Eye Institute, Oregon Health & Science University, Portland, OR
  • Footnotes
    Commercial Relationships James Rosenbaum, Genentech (C), Abbott (F), Xoma (C), Eyegate (F), Bristol Myers (F), Lux (C), Novartis (C), Regeneron (C), Teva (C), Therakine (F), Mitotech (F), Aquinox (F), Allergan (C), Santen (C); Dongseok Choi, None; Christina Harrington, None; Gerald Harris, None; Craig Czyz, None; Valerie White, None; Eric Steele, None; Bobby Korn, None; David Wilson, None; Stephen Planck, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2035. doi:
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      James Rosenbaum, Dongseok Choi, Christina Harrington, Gerald Harris, Craig Czyz, Valerie White, Eric Steele, Bobby Korn, David Wilson, Stephen Planck; Identifying and classifying nonspecific orbital inflammation (NSOI) by gene expression array. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2035.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: NSOI is presumed to be a heterogeneous collection of diseases that are difficult to classify by conventional histology and sometimes difficult to distinguish from other causes of orbital inflammation.

Methods: We analyzed mRNA from 38 formalin-fixed anterior orbital biopsies taken from 14 patients with NSOI, 12 patients with thyroid eye disease (TED), 2 patients with granulomatosis with polyangiitis, and 4 patients with sarcoidosis as well as 6 biopsies from healthy controls. Gene expression was analyzed with Affymetrix Gene Chip U133 plus 2.0 arrays that detect approximately 47,400 transcripts.

Results: Principal coordinate analysis indicated that NSOI demonstrated disease heterogeneity which could be readily distinguished from controls or tissues from patients with other orbital diseases. 230 genes were expressed at least two-fold greater than in control tissue using a false discovery rate (FDR)<0.05 and 1930 genes were reduced by at least two fold relative to controls with an FDR <0.05. All of the 25 probe sets with signals most enhanced in tissue from patients with NSOI were immunoglobulin related. Other prominently upregulated genes included CXCR4, YKL-40, SLAM Family 7, CXCL9, and IL-7 receptor. Prominently down regulated genes included alcohol dehydrogenase 1B, perilipin 1, adiponectin, leptin receptor, and C1Q. Many transcripts were up or down regulated by ten-fold or more compared to normal tissue. Transcripts detected by 6839 probe sets were differentially regulated in NSOI (FDR <0.05; >1.5-fold change) compared to either TED or sarcoid tissues.

Conclusions: We believe that this is the first study to analyze gene expression from patients with NSOI and the first study to compare gene expression among orbital diseases. Transcripts related to inflammation often distinguished NSOI from normal tissue. Our results support the hypothesis that gene expression array will become an essential tool in the classification and understanding of NSOI.

Keywords: 631 orbit • 557 inflammation • 535 gene microarray  
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